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2007 Program and Abstracts | 2007 Posters
Identification of a Novel Kindred with Familial Pancreatitis and Pancreatic Cancer
Jennifer Lafemina*1, Penelope Roberts2, Yin Hung1, Dushyant Sahani3, James Gusella2, Carlos Fernandez-Del Castillo1, Andrew Warshaw1, Sarah P. Thayer1
1Surgery, Massachusetts General Hospital, Boston, MA; 2Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA; 3Radiology, Massachusetts General Hospital, Boston, MA

OBJECTIVES: Familial pancreatic cancer comprises 5-10% of pancreatic cancer cases. The genes responsible are now being described and characterized, but remain poorly understood. One subtype of this syndrome is a combined phenotype of pancreatitis and pancreatic cancer. Mutations in the cationic trypsinogen (PRSS1) and SPINK1 genes have been associated with hereditary pancreatitis and pancreatic cancer phenotypes. Here we describe a recently identified family, Family Pancreatitis/Pancreatic Cancer (Family P/PC), which demonstrates pancreatitis and pancreatic cancer due to a previously uncharacterized genetic mutation.
Methods:Subjects complete a questionnaire about demographics, medical problems, signs and symptoms of pancreatic disease, family history, and relevant social history. Laboratory, radiologic and endoscopic evaluations are used to identify possible genetic carriers. Selected patients are screened for genetic mutations that have been linked to hereditary cancer syndromes predisposing to pancreatic cancer and syndromes associated with hereditary pancreatitis and/or pancreatic cancer.
Results:There are 140 known members of Family P/PC, of whom 81 were included in a pedigree. There were 12 children in Generation II, 7 of whom have pancreatitis. Four of the 7 developed pancreatic cancer. Mean age at diagnosis of cancer was 59 years. The presentation of pancreatitis has been variable and subtle. Age of presentation varies greatly; earliest diagnosis of pancreatitis was at 5 years old. Although many patients with pancreatitis have subtle clinical symptoms, they do have detectable abnormalities in their pancreatic enzymes and CT evidence consistent with chronic pancreatitis. One affected family member was also diagnosed with breast cancer. No other cancers have been identified in the family. Affected members underwent genetic testing for genetic mutations associated with pancreatitis and pancreatic cancer phenotypes—BRCA1, BRCA2, CFTR, SPINK1, and PRSS1. Full sequence analyses of these genes failed to reveal mutations or polymorphisms.
Conclusions:Based on the pedigree of Family P/PC and preliminary analysis of DNA, we believe that the members of Family P/PC carry a novel genetic mutation resulting in hereditary pancreatitis and pancreatic cancer. We believe that the genetic mutation is transmitted in an autosomal dominant pattern, is expressed with high penetrance, and is part of a unique familial pancreatic disease syndrome. Identification of the genetic locus may give us further insignts into the molecular mechanisms that regulate pancreatic function and that contribute to hereditary and sporadic pancreatic disease predisposition.


2007 Program and Abstracts | 2007 Posters
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